Abstract
Simple SummaryDNA vaccination represents a useful approach for human papillomavirus (HPV) cancer therapy. The therapeutic potential of plant-based natural compounds for control of HPV- associated cancers has been also widely explored. Genetic vaccines for HPV-associated tumors that include plant protein-encoding gene sequences, used alone or in combinations with plant metabolites, are being investigated but are still in their infancy. Main focus of this paper is to provide an overview of the current state of novel therapeutic strategies employing genetic vaccines along with plant-derived compounds and genes. We highlight the importance of multimodality treatment regimen such as combining immunotherapy with plant-derived agents.Antigen-specific immunotherapy and, in particular, DNA vaccination provides an established approach for tackling human papillomavirus (HPV) cancers at different stages. DNA vaccines are stable and have a cost-effective production. Their intrinsic low immunogenicity has been improved by several strategies with some success, including fusion of HPV antigens with plant gene sequences. Another approach for the control of HPV cancers is the use of natural immunomodulatory agents like those derived from plants, that are able to interfere in carcinogenesis by modulating many different cellular pathways and, in some instances, to reduce chemo- and radiotherapy resistance of tumors. Indeed, plant-derived compounds represent, in many cases, an abundantly available, cost-effective source of molecules that can be either harvested directly in nature or obtained from plant cell cultures. In this review, an overview of the most relevant data reported in literature on the use of plant natural compounds and genetic vaccines that include plant-derived sequences against HPV tumors is provided. The purpose is also to highlight the still under-explored potential of multimodal treatments implying DNA vaccination along with plant-derived agents.
Highlights
Cancer is considered the leading cause of death in wealthy countries, and 15–20% of all human cancers are associated with viral infections [1,2]
Since most cancers develop in decades after the initial human papillomavirus (HPV) infection, the impact of this vaccination program will only be seen in the long-term
The combination of natural compounds with chemotherapy and radiotherapy in the treatment of cervical cancer was reported to improve in some cases sensitization of HPV cancer cells and to minimize the toxicity of these therapies (Table 2)
Summary
Cancer is considered the leading cause of death in wealthy countries, and 15–20% of all human cancers are associated with viral infections [1,2]. We described that a plant extract of Nicotiana benthamiana, containing ectopically expressed HPV 16 E7 protein, induced a cell-mediated immune response able to protect vaccinated mice from tumor challenge, notably without any adjuvant [10,11]. A plant signal sequence fused to synthetic E7 and L2 (i.e., the minor HPV capsid protein) genes of HPV 16 was able to elicit strong specific IgG humoral responses associated to E7 specific T-cell mediated immunity [19,20] This chimeric vaccine, with preventive and therapeutic effects against HPV infections, offers excellent prospects for the future of DNA vaccine research. We focus on the most relevant aspects of plant-derived compounds and genetic vaccines that might be decisive for the future development of cost-effective HPV vaccines
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